Glutamatergic pathways as a target for the treatment of dyskinesias in Parkinson's disease
Glutamatergic pathways as a target for the treatment of dyskinesias in Parkinson's disease
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DOI：
10.1042/bst20140006
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发表时间：
2014-04-01
影响因子：
3.9
通讯作者：
Cenci, M. Angela
中科院分区：
文献类型：
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作者：
Cenci, M. Angela
PD（帕金森病）的特点是一些典型的运动特征，这些特征是由纹状体多巴胺耗竭引起的，并且对左旋多巴的多巴胺替代疗法反应良好。不幸的是，大多数接受左旋多巴治疗的帕金森病患者在几年内就会出现异常的不自主运动（运动障碍）。 LID（左旋多巴诱发的运动障碍）发生的机制一方面涉及多巴胺释放和清除的突触前失调，另一方面涉及大脑中对多巴胺的异常突触后反应。有大量证据表明这些多巴胺依赖性机制受到谷氨酸能途径和谷氨酸受体的调节。本文总结了谷氨酸能通路在 LID 中的病理生理学作用，并回顾了使用不同类别和亚型谷氨酸受体的药理学调节剂治疗帕金森运动障碍所获得的临床前和临床结果。
PD (Parkinson's disease) is characterized by some typical motor features that are caused by striatal dopamine depletion and respond well to dopamine-replacement therapy with L-dopa. Unfortunately, the majority of PD patients treated with L-dopa develop abnormal involuntary movements (dyskinesias) within a few years. The mechanisms underlying the development of LIDs (L-dopa-induced dyskinesias) involve, on one hand, a presynaptic dysregulation of dopamine release and clearance and, on the other hand, an abnormal postsynaptic response to dopamine in the brain. There is a large amount of evidence that these dopamine-dependent mechanisms are modulated by glutamatergic pathways and glutamate receptors. The present article summarizes the pathophysiological role of glutamatergic pathways in LID and reviews pre-clinical and clinical results obtained using pharmacological modulators of different classes and subtypes of glutamate receptors to treat parkinsonian dyskinesias.